Sertraline

ZoloftLustralSertraline HydrochlorideHistorySertraline (Zoloft)
Sertraline, sold under the trade name Zoloft among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class.wikipedia
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Antidepressant

antidepressantsanti-depressantanti-depressants
Sertraline, sold under the trade name Zoloft among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class.
This leaves out SSRIs such as paroxetine, sertraline and fluvoxamine CR as acceptable and tolerated treatment options for this disorder.

Selective serotonin reuptake inhibitor

SSRIselective serotonin reuptake inhibitorsSSRIs
Sertraline, sold under the trade name Zoloft among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class.
Paroxetine was the first drug to be approved for social anxiety disorder and it is considered effective for this disorder, sertraline and fluvoxamine were later approved for it too, escitalopram and citalopram are used off label with acceptable efficacy, while fluoxetine is not considered to be effective for this disorder.

Clomipramine

Anafranilchlorimipramineclomipramine hydrochloride
In line with this generalization, sertraline was no better than placebo in inpatients (see History) and as effective as the TCA clomipramine for severe depression.
In a meta-analysis of various trials involving fluoxetine (Prozac), fluvoxamine (Luvox), and sertraline (Zoloft) to test their relative efficacies in treating OCD, clomipramine was found to be the most effective.

Bupropion

WellbutrinZybanAplenzin
Comparative clinical trials demonstrated that sertraline is similar in efficacy against depression to moclobemide, nefazodone, escitalopram, bupropion, citalopram, fluvoxamine, paroxetine, and mirtazapine.
A meta-analysis from 2009 found that bupropion is as effective as several other widely prescribed drugs, including fluoxetine and paroxetine, although trends favoring the efficacy of escitalopram, sertraline, and venlafaxine over bupropion have been observed.

Serotonin

5-HTserotonergic5-hydroxytryptamine
Sertraline is believed to work by increasing serotonin effects in the brain.
However, the PMAT, despite its relatively low serotonergic affinity, has a considerably higher transport 'capacity' than SERT, "resulting in roughly comparable uptake efficiencies to SERT in heterologous expression systems.” The study also suggests some SSRIs, such as fluoxetine and sertraline anti-depressants, inhibit PMAT but at IC 50 values which surpass the therapeutic plasma concentrations by up to four orders of magnitude. Therefore, SSRI monotherapy is "ineffective" in PMAT inhibition. At present, no known pharmaceuticals are known to appreciably inhibit PMAT at normal therapeutic doses. The PMAT also suggestively transports dopamine and norepinephrine, albeit at K m values even higher than that of 5-HT (330–15,000 μmoles/L).

Citalopram

CelexaCipramilTalohexal
Comparative clinical trials demonstrated that sertraline is similar in efficacy against depression to moclobemide, nefazodone, escitalopram, bupropion, citalopram, fluvoxamine, paroxetine, and mirtazapine.
In the National Institute for Health and Clinical Excellence ranking of 10 antidepressants for efficacy and cost-effectiveness citalopram is fifth in effectiveness (after mirtazapine, escitalopram, venlafaxine, and sertraline) and fourth in cost-effectiveness.

Fluoxetine

ProzacProzakSarafem
There is low quality evidence that sertraline is more efficacious for the treatment of depression than fluoxetine.
Sertraline is often the preferred SSRI during pregnancy due to the relatively minimal fetal exposure observed and its safety profile while breastfeeding.

Reboxetine

Reboxetine was significantly worse.
Reboxetine is an intermediate-level inhibitor of P-glycoprotein, which gives it the potential to interact with ciclosporin, tacrolimus, paroxetine, sertraline, quinidine, fluoxetine, fluvoxamine.

Posttraumatic stress disorder

post-traumatic stress disorderPTSDpost traumatic stress disorder
It is used to treat major depressive disorder, obsessive–compulsive disorder, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder, and social anxiety disorder.
Evidence provides support for a small or modest improvement with sertraline, fluoxetine, paroxetine, and venlafaxine.

Major depressive disorder

depressionclinical depressionmajor depression
It is used to treat major depressive disorder, obsessive–compulsive disorder, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder, and social anxiety disorder.
A review commissioned by the National Institute for Health and Care Excellence (UK) concluded that there is strong evidence that selective serotonin reuptake inhibitors (SSRIs), such as escitalopram, paroxetine, and sertraline, have greater efficacy than placebo on achieving a 50% reduction in depression scores in moderate and severe major depression, and that there is some evidence for a similar effect in mild depression.

Paroxetine

PaxilSeroxatparoxetine hydrochloride
Comparative clinical trials demonstrated that sertraline is similar in efficacy against depression to moclobemide, nefazodone, escitalopram, bupropion, citalopram, fluvoxamine, paroxetine, and mirtazapine. It is unclear if sertraline is any different from another SSRI, paroxetine, for depression; though escitalopram may have some benefits over sertraline.
Along with the other SSRIs, sertraline and fluoxetine, paroxetine is considered a low-risk drug in cases of overdose.

Premenstrual dysphoric disorder

PMDDdysphoric disorderpremenstrual dysphoric disorder (PMDD)
It is used to treat major depressive disorder, obsessive–compulsive disorder, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder, and social anxiety disorder.
The U.S. Food and Drug Administration (FDA) has approved four SSRIs for the treatment of PMDD: Fluoxetine (available as generic or as Prozac or Sarafem), sertraline (Zoloft), paroxetine (Paxil), and escitalopram oxalate (Lexapro).

Pfizer

Pfizer Inc.Pfizer, Inc.Pfizer Inc
Sertraline was approved for medical use in the United States in 1991 and initially sold by Pfizer.

Social anxiety disorder

social phobiaAnthropophobiasociophobia
It is used to treat major depressive disorder, obsessive–compulsive disorder, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder, and social anxiety disorder.
Paroxetine, sertraline and fluvoxamine are three SSRIs that have been approved by the FDA to treat social anxiety disorder.

Fluvoxamine

Luvox
Comparative clinical trials demonstrated that sertraline is similar in efficacy against depression to moclobemide, nefazodone, escitalopram, bupropion, citalopram, fluvoxamine, paroxetine, and mirtazapine.

CYP3A4

cytochrome P450 3A43A4cytochrome P450-3A4
Accordingly, in human trials it caused increased blood levels of CYP2D6 substrates such as metoprolol, dextromethorphan, desipramine, imipramine and nortriptyline, as well as the CYP3A4/CYP2D6 substrate haloperidol.

CYP2B6

2B6CYP2B6 inhibitors
Sertraline is a moderate inhibitor of CYP2D6 and CYP2B6 in vitro.

Premenstrual syndrome

PMSpremenstrual stress syndromepremenstrual tension
SSRIs, including sertraline, reduce the symptoms of premenstrual syndrome.
SSRIs like fluoxetine, sertraline can be used to treat severe PMS.

Tametraline

Tametraline (CP-24,441), a very close analogue of sertraline and the compound from which sertraline was originally derived, is an NDRI that was never marketed.
Tametraline (CP-24,441) is the parent of a series of chemical compounds investigated at Pfizer that eventually led to the development of sertraline (CP-51,974-1).

5-HT2C receptor

5-HT 2C 5-HT 2C receptor5HT 2C
Activation of 5-HT 2C by serotonin is responsible for many of the negative side effects of SSRI and SNRI medications, such as sertraline, paroxetine, venlafaxine, and others.

CYP2D6

2D6cytochrome P450 2D6cytochrome p-450 cyp2d6
Accordingly, in human trials it caused increased blood levels of CYP2D6 substrates such as metoprolol, dextromethorphan, desipramine, imipramine and nortriptyline, as well as the CYP3A4/CYP2D6 substrate haloperidol. Sertraline is a moderate inhibitor of CYP2D6 and CYP2B6 in vitro.

Serotonin reuptake inhibitor

serotoninSRIserotonin reuptake inhibition
Sertraline acts as a potent serotonin reuptake inhibitor (SRI), with an affinity (K i ) for the serotonin transporter (SERT) of 0.4 nM and an IC 50 value of 2.8 nM, according to a couple of studies.

Kenneth Koe

B. Kenneth KoeKen Koe
A few years later, in 1977, pharmacologist Kenneth Koe, after comparing the structural features of a variety of reuptake inhibitors, became interested in the tametraline series.
He and Willard Welch developed sertraline, which was branded and sold as Zoloft by his longtime employer Pfizer starting in 1991.

Desmethylsertraline

The major metabolite of sertraline, desmethylsertraline, is about 50 times weaker as a serotonin transporter inhibitor than sertraline and its clinical effect is negligible.
Desmethylsertraline (DMS), also known as norsertraline, is an active metabolite of the antidepressant drug sertraline.

CYP2C9

2C9cytochrome P450 2C9CYP 2C9
Sertraline had a slight inhibitory effect on the metabolism of diazepam, tolbutamide and warfarin, which are CYP2C9 or CYP2C19 substrates; this effect was not considered to be clinically relevant.